Please use this identifier to cite or link to this item:
https://hdl.handle.net/2445/177852
Title: | RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness |
Author: | Benítez, Sandra Cordero, Alex Santamaría, Patricia G. Redondo Pedraza, Jaime Rocha, Ana S. Collado-Solé, Alejandro Jimenez, Maria Sanz Moreno, Adrian Yoldi, Guillermo Santos, Juliana C. Benedictis, Ilaria De Gómez Aleza, Clara Silva Álvarez, Sabela Da Troulé, Kevin Gómez López, Gonzalo Alcazar, Noelia Palmero, Ignacio Collado, Manuel Serrano Marugán, Manuel González Suárez, Eva |
Keywords: | Càncer de mama Metàstasi Cicle cel·lular Breast cancer Metastasis Cell cycle |
Issue Date: | 1-Jan-2021 |
Publisher: | Elsevier Inc. |
Abstract: | Rank signaling enhances stemness in mouse and human mammary epithelial cells (MECs) and mediates mammary tumor initiation. Mammary tumors initiated by oncogenes or carcinogen exposure display high levels of Rank and Rank pathway inhibitors have emerged as a new strategy for breast cancer prevention and treatment. Here, we show that ectopic Rank expression in the mammary epithelia unexpectedly delays tumor onset and reduces tumor incidence in the oncogene-driven Neu and PyMT models. Mechanistically, we have found that ectopic expression of Rank or exposure to Rankl induces senescence, even in the absence of other oncogenic mutations. Rank leads to DNA damage and senescence through p16/p19. Moreover, RANK-induced senescence is essential for Rank-driven stemness, and although initially translates into delayed tumor growth, eventually promotes tumor progression and metastasis. We uncover a dual role for Rank in the mammary epithelia: Rank induces senescence and stemness, delaying tumor initiation but increasing tumor aggressiveness. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.devcel.2021.04.022 |
It is part of: | Developmental Cell, 2021, vol. 56 |
URI: | https://hdl.handle.net/2445/177852 |
Related resource: | https://doi.org/10.1016/j.devcel.2021.04.022 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Publicacions de projectes de recerca finançats per la UE Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
12541_6516973_benitez_et_al_dev_cell_2021.pdf | 4.32 MB | Adobe PDF | View/Open |
This item is licensed under a
Creative Commons License